Imidazolines



Patented June 13, 19 39 UNITED STATES 2,161,938 PATENT OFFICEIIVHDAZOLINES Adolf Sonn, Konigsberg, Germany, assignor to the firmSociety of Chemical Industry in Basie,

Basel, Switzerland No Drawing. Application February 25, 1938, Se-

rial No. 192,645. In

4 Claims.

O R1 wherein R has the signification indicated above and R1 stands foran alkyl radical, to react with ethylene diamine.

The iminoethers may be caused to react with ethylene diamine in the formof free bases or as salts of mineral acids, in the presence or absenceof a solvent such as alkanols or alkyl polyhalides at room temperatureor at a raised temperature. When the reaction is carried out at lowtemperature and particularly when using free iminoethers, a neutral gasis preferably passed through the composition for the purpose of removingthe ammonia formed in the course of the reaction. When using a freeiminoether and in the absence of a solvent, the crude imidazoline isobtained directly after the reaction is at an end, which can berecognized by the discontinuation of the evolution of ammonia. The crudeimidazoline can be purified by distillation or crystallization. Whenusing however a salt of an iminoether as well as a solvent, the solventis distilled when the evolution of ammonia is finished, the residue isrecrystallized or mixed with a strong lye and extracted with an organicsolvent insoluble in water. After drying the solution of the extractionwith one of the usual alkaline drying agents, the solvent is expelledand the residual imidazoline base is either distilled or recrystallized.

The iminoethers Used as parent materials are produced from thecorresponding nitriles by dissolving the latter in alkanols or-in otherorganic solvents to which an alkanol has been added, mixing them at lowtemperature with a mineral acid and allowing them to stand for severalhours. The solvent is then expelled under reduced pressure at as low atemperature as possible and there remains the salt of the iminoether.

It is known to produce 2-alkyl-imidazolines by heating the salts ofaliphatic 1:2-diamines with salts of fatty acids [Ladenburg, Berichteder Germany July 31, 1934 deutschen chemischen Gesellschaft, vol. 27,pages 2952-57 (1894), Klingenstein, 10c. cit. vol. 28, pages 1173-76(1895) l. 2-phenylor 2-naphthyl-imidazoline can for example be obtainedby causing thiobenzamide to react with ethylene diamine [G. Forssel,loc. cit. vol. 25, pages 2132-42 (1892) l or by the action ofbenzimino-ethylether on bromethylamine hydrobromide in the presence ofsodium alcoholate [Stoll et al., Journal fiir praktische Chemie, vol.140, page 60 (1934)]. Compounds of the kind indicated above are alsoobtained by the action of iminoethers of higher fatty acids on diamines[Bockmiihl et al., U. S.

Patent 1,958,529 (1934) 1. Further it is known to obtain-glyoxalidine-arylmethylols by the action of alkylene diamines oniminoethers of substituted mandelic acids [Bockmiihl et al., U. S.Patent 1,999,989 (1935)].

The new compounds, the salts of which are-all easily soluble in water,have essential pharmacological advantages over the known compoundsindicated above. Thus, for example, the blood pressure of the rabbit isincreased to a much greater extent.

The following examples illustrate the invention, the parts being byweight:

Example 1 The phenyl-acetiminoether hydrochloride of the formula NH.HG1

GHsCHzC from 12 parts of benzylcyanide is mixed with 8 parts ofethylene-diamine hydrate which has been diluted with little alcohol,whereby the crystals go into solution. The whole is then heated on thewater-bath until the ammonia odor has disappeared, cooled, concentratedcaustic potash solution added, and the separated oil extracted withether. The solution is dried with potassium carbonate and potassiumhydroxide. After evaporation a pale oil is left which distills at 147 C.under a pressure of 9 mm. and which solidifies in the condenser to aWhite crystalline mass. The yield amounts to 90 per cent. of the theory.The hydrochloride melts at 168-170 C. This product has the formulaInstead of alcohol, chloroform may also be used as solvent. One may,however, just as well renounce to the solvent.

Instead of the hydrochloride, the sulfate of the iminoether may also beused.

In similar manner like the benzylimidazoline described above, there mayalso be produced a1- kylben zylimidazolines, such as-for exampledimethylbenzylimidazoline; ethylbenzylimidazoline,

propylbenzylimidazoline.

Example 2 3 partsof"3:4:5-trimethoxyphenyl-acetiminoethyletherhydrochloride ofthe'formula (of melting point 114-115 C. with decomposition, producedfrom 3 4 5-trimethoxy-phenylacetonitrile) are dissolved in 15 parts ofabsolute alcohol. 1 part of the ethylene diamine is added fairlyquickly; and the mixture is slowly heated to 80 C. and maintained atthis temperature for some hours. 'T'he alcohol is then expelled'and theresidue, is mixed with dilute caustic soda solution and thoroughlyextracted with benzene. After drying over, potash the residue is.distilled under a pressure or 0115 mm." The 2-(3':4:5-trimethoxybenzyl)-imidazoline of the formula a-colorless crystalline mass of boilingpoint HOV-171 C. .under 0.15 mm. pressure and of melting point 76'77 C..The hydrochloride is a colorless crystalline powder of melting point185- 186 C. r

Instead of the hydrochloride of the3=4;5-mmethoxy-phenyl-acetimino-ethylether there may be used just aswell also another. hydrohalide.

In similar manner there may also beproduced otheralkoxy-benzylimidazolines, such as ethoxy, propyloxy-,butyloxy-benzyl-imidazolines,

Example 3 [2.7 parts of 4-methoxy-naphthyl-(l)-acetiminoethyletherhydrochloride oi the formula NH.HC1

' GHPC O CaHs I 'OCHa (produced from 4-methoxy-naphthyl-(D-acetonitrile) are dissolved in 12 parts of absolute alcohol. 1 part of'ethylenediamine is then added and the whole is heated to gentle boilingwhile passing it through nitrogen. and simultaneously stirring untilammonia escapes no longer. The 7 alcohol is then distilled and theresidue 'mixed with 40 parts, of benzene and 1:8 partsof'caustic potash.Stirring is continued for some time whereby thei'midazoline base isdissolved in' benzene. The benzene residue. is recrystallized sev- Veral times from toluene. The'2-[4-methoxynaphthyl-(l)-methyl]-imidazo1ine of the formula V h 1/N-CH:

NH Ha 7 represents colorless. crystals of melting point 123- 124 C. .Itshydrochloride is easily soluble in water. 7

According to this process there may also be produced hYdTO'XY", alkyl-,and other alkoxy- V naphthylmethylimidazolines.

In analogous manner there may for example also be produced the followingcompounds:-

. 2-[4'-oxybenzyl]-imidazoline, melting point of the hydrochloride186-187 C.; 2- [3' :4 :5-t-rioxy-benzyll -imidazoline, melting point ofthe-hydrochloride 203-205 C.; 2-[4'-methoxy-benzyl]-imidazoline ofmelting point 1l8-120 0.;

2-[3:4-dimethoxy benzyll -imidazoline, melting point of thehydrochloride 210'-211 C.;

2 3' :4'- methylenedioxy -benzyl] imidazoli-ne, 7

2- [alkoxy quinoline- (8") methyl] -imidazolines,

linemethylimidazolines.

What I claim is: 1. The compounds of the formula N-CH2 wherein'R standsfor a member of the group consisting of substituted and unsubstitutedphenylmethyl, naphthylmethyl and ,quinoline-C methyl radicals, thesubstituent being a member of the group consisting of hydroxy, alkoxyand alkyl; the methyl group of said substitutedand unsubstitutedphenylmethyl, naphthyl methyl and quinoline-C-m'ethyl radicals beingunsubstituted:

2. The compound of the formula l a and corresponding hydroxye andalkyl-quino'e forming a hydrochloride of melting point 185- 3. Thecompounds of the formula N-CH2 4'. The compound of the formula 7 formingcrystals of melting point 123-124 C. v

ADOLF SONNY

